Consolidation Immunotherapy after Chemoradiation Mitigates Impact of Radiation Induced Lymphopenia on Survival in Non-Small Cell Lung Cancer Patients

Abstract

Previously, we showed that severe radiation-induced lymphopenia (RIL) is associated with poorer survival in locally advanced non-small cell lung cancer treated with chemoradiation (CRT). However, the prognostic role of RIL in NSCLC treated with CRT followed by consolidative immunotherapy (IO) is unknown. Patients treated with concurrent CRT ± IO as consolidation therapy for between 2010 and 2019 were retrospectively reviewed. IO was administrated monthly up to 1 year. The values of absolute lymphocyte counts (ALC) were collected weekly during thoracic radiation. Grade 4 lymphopenia (G4L) was defined as an ALC nadir < 0.2 × 103/ul based on CTCAE 5.0. 2-year overall survival (OS) was measured from the end of CRT. 2-year OS of patients who received CRT or CRT- IO were compared by Cox proportional hazard regression and Kaplan-Meier analysis. The thresholds for covariate selection in multi-variate analysis are 0.2 for inclusion and 0.1 for removal. All statistics were performed using SPSS with 0.05 as a significance level. A total of 358 patients were included, 233 received CRT and 125 received CRT-IO. Majority of patients were white (87%), prior/current smokers (86%) and had stage III disease (82%). Patient and tumor related characteristics were well-balanced. In CRT-IO group, fewer patients were treated by protons (11% vs. 29%) and had radiation dose > 66Gy (16% vs. 46%) compared to the CRT group. Overall, G4L developed in 25% (n = 89) of patients, with 67 (28%) in CRT alone and 22 (18%) in CRT-IO (p = 0.02). In CRT group, the 2-year survival rate of patients with G4L (49%) was lower than that of patients without G4L (65%) (p = 0.032). In the CRT-IO group, however, no significant differences in 2-year survival was found in patients with G4L (82%) or without G4L (89%) (p = 0.213). While G4L was associated with poorer survival in patients treated with CRT alone, consolidative IO appears to mitigated the negative impact of G4L on survival with improved short-term survival in all patients regardless of lymphopenia status. The mechanistic underpinnings of these findings will need to be explored.